The overall objective of this research is to learn the detailed mechanism of action of those metal-activated and metalloenzymes which catalyze two broad classes of reactions: (1) reactions of ATP; (2) polarization of carbonyl groups nucleotidyl groups (DNA and RNA polymerases), pyrophosphoryl groups (P-Rib-PP synthetase, thiamine pyrophosphokinase, dihydropteridine pyrophosphokinase), phosphoryl groups (pyruvate kinase, protein kinase, adenylate kinase, P-enolpyruvate carboxylase) and the polarization of substrate carbonyl groups (yeast aldolase). The purpose of studying a wide range of chemically related enzyme catalyzed reactions is to seek general prinicples of enzyme chemistry. In addition, certain other metalloenzymes which have obscure mechanisms requiring further elucidation are being studied (catalase, diol dehydrase, urease).